Glucose Metabolism Becomes Insufficient to Meet the Energy Demands of the Aging Hippocampus

Recent research has suggested that the hippocampus, vital to memory function, has evolved to operate at the upper edge of its normal supply of nutrients and energy. Even minor reductions to that supply will produce functional issues in memory, and there are many mechanisms by which aging reduces the supply of nutrients and energy to the brain.

Reduced blood flow is one important factor, due to loss of capillary density, vascular dysfunction, lack of fitness, heart failure, and so forth. The paper here is an interesting read in this context, looking at loss of efficiency in glucose metabolism in the aging hippocampus. The brain obtains most of its energy from processing of glucose, and disruption might be expected to produce negative consequences.

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Aging is a process that adversely affects brain functions such as cognition. Brain activity is highly energy consuming, with glucose serving as the main energy source under normal circumstances. Whether the dynamics of glucose metabolism change with aging is not well understood. This study sought to investigate the activity-dependent changes in glucose metabolism of the mouse hippocampus during aging. In brief, after 1 hour of contextual exploration in an enriched environmental condition or 1 hour in a familiar home cage condition, metabolites were measured from the hippocampus of both young adult and aged mice with metabolomic profiling.

Compared to the home cage context, the enriched contextual exploration condition resulted in changes in the concentration of 11 glucose metabolism-related metabolites in the young adult hippocampus. In contrast, glucose metabolism-related metabolite changes were more apparent in the aged group altered by contextual exploration when compared to those in the home cage condition. Importantly, in the aged groups, several key metabolites involved in glycolysis, the TCA cycle, and ketone body metabolism accumulated, suggesting the less efficient metabolization of glucose-based energy resources. Altogether, the analyses revealed that in the aged mice altered by enriched contextual exploration, the glucose resource seems to be unable to provide enough energy for hippocampal function.